Trends in Genetics
Volume 18, Issue 9, 1 September 2002, Pages 479-485
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Review
Checking cell size in yeast

https://doi.org/10.1016/S0168-9525(02)02745-2Get rights and content

Abstract

To remain viable, cells have to coordinate cell growth with cell division. In yeast, this occurs at two control points: the boundaries between G1 and S phases, also known as Start, and between G2 and M phases. Theoretically, coordination can be achieved by independent regulation of growth and division, or by participation of surveillance mechanisms in which cell size feeds back into cell-cycle control. This article discusses recent advances in the identification of sizing mechanisms in budding and in fission yeast, and how these mechanisms integrate with environmental stimuli. A comparison of the G1–S and G2–M size-control modules in the two species reveals a degree of conservation higher than previously thought. This reinforces the notion that internal sizing could be a conserved feature of cell-cycle control throughout eukaryotes.

Section snippets

Size control at Start: budding yeast

How does budding yeast measure its size, and how does this control Start? The G1–S size-control module is presented in Fig. 2. Its core consists of three G1 cyclins (Cln1–3) and two B-type cyclins (Clb5 and Clb6). These cyclins bind to a CDK1 homolog, Cdc28 (Table 1), and target its activity towards specific sets of substrates. The level of Cln3 is important for timely expression of the CLN1 and CLN2 genes. The resulting increase in the activity of Cln1– and Cln2–Cdc28 complexes is responsible

Size control at Start: fission yeast

In fission yeast, Start is initiated by a CDK1 homolog, Cdc2, in association with a G1 cyclin, Puc1, and three B-type cyclins, Cig1, Cig2 and Cdc13. Two inhibitory mechanisms prevent premature initiation of S phase: one involves a CDK inhibitor, Rum1, and the other involves a component of the ubiquitin proteolysis machinery, Ste9. The wiring diagram reveals striking similarity between fission yeast and budding yeast (Fig. 3, Table 1) [9]. As already mentioned, the fission yeast G1–S size

Size control at G2–M: fission yeast

The wee1 gene was isolated as the prototype cell-size mutant that enters mitosis precociously and loses the wild-type ability to modify cell size at mitosis in response to the availability of nitrogen [9]. As cells progress through S and G2, Cdc13 slowly accumulates, but the associated Cdc2 activity remains inhibited by Wee1-dependent tyrosine phosphorylation (Fig. 4a). A Wee1 inhibitory kinase, Cdr1, is probably a component of the nutrition-sensing module (Fig. 1a, process 1) as cdr1-deficient

Size control in G2–M: budding yeast

In G2, Cdc28 is phosphorylated by the Wee1 homolog Swe1, and dephosphorylated by the Cdc25 homolog Mih1 [8] (Fig. 4b, Table 1). Unlike their counterparts in fission yeast, however, neither of these components are essential in budding yeast. It has been proposed that instead of size control, Clb2–Cdc28 tyrosine phosphorylation evolved a specialized function in execution of a morphogenesis checkpoint. The checkpoint is activated when cells fail to form a bud or when the integrity of the actin

Concluding remarks

What is ‘cell size’? Entirely in accord with Pringle and Hartwell [10], I use this deliberately vague expression instead of more specific terms simply because we are still far from fully understanding what represents cell size within cells. Production of Cln3 is clearly dependent on the total number of ribosomes in the cytoplasm, which increases as cells grow, but other possible sizers do not offer such clear-cut solutions. Protein mass, the number of ribosomes and cell volume are obvious

Acknowledgements

I thank E. Boye, L. Breeden, B. Futcher, D. Kellogg, D. Lew, S. Moreno and A. Sveiczer for fruitful discussions and for sharing their data before publication. I also thank P. Young, J. Karagiannis and D. Kellogg for critical reading of the manuscript.

References (70)

  • P. Russell

    Conservation of mitotic controls in fission and budding yeast

    Cell

    (1989)
  • H.H. McAdams et al.

    It's a noisy business! Genetic regulation at the nanomolar scale

    Trends Genet.

    (1999)
  • C.M. Coelho et al.

    Do growth and cell division rates determine cell size in multicellular organisms?

    J. Cell Sci.

    (2000)
  • M. Sipiczki

    Where does fission yeast sit on the tree of life?

    Genome Biol. , .1–1011.4

    (2000)
  • D. Lew

    Cell cycle control in Saccharomyces cerevisiae

  • S.A. MacNeill et al.

    Cell cycle control in fission yeast

  • J.R. Pringle et al.

    The Saccharomyces cerevisiae cell cycle

  • A. Sveiczer

    The size control of fission yeast revisited

    J. Cell Sci.

    (1996)
  • B. Futcher

    Cyclins and the wiring of the yeast cell cycle

    Yeast

    (1996)
  • D.D. Hall

    Regulation of the Cln3–Cdc28 kinase by cAMP in Saccharomyces cerevisiae

    EMBO J.

    (1998)
  • C. Gallego

    The Cln3 cyclin is down-regulated by translational repression and degradation during the G1 arrest caused by nitrogen deprivation in budding yeast

    EMBO J.

    (1997)
  • F. Parviz et al.

    Transcriptional regulation of CLN3 expression by glucose in Saccharomyces cerevisiae

    J. Bacteriol.

    (1998)
  • L.L. Newcomb

    AZF1 is a glucose-dependent positive regulator of CLN3 transcription in Saccharomyces cerevisiae

    Mol. Cell. Biol.

    (2002)
  • M. Polymenis et al.

    Coupling of cell division to cell growth by translational control of the G1 cyclin CLN3 in yeast

    Genes Dev.

    (1997)
  • C. Berset

    The TOR (target of rapamycin) signal transduction pathway regulates the stability of translation initiation factor eIF4G in the yeast Saccharomyces cerevisiae

    Proc. Natl. Acad. Sci. U. S. A.

    (1998)
  • P. Danaie

    CLN3 expression is sufficient to restore G1-to-S-phase progression in Saccharomyces cerevisiae mutants defective in translation initiation factor eIF4E

    Biochem. J.

    (1999)
  • E. Garı́

    Whi3 binds the mRNA of the G1 cyclin CLN3 to modulate cell fate in budding yeast

    Genes Dev.

    (2001)
  • M. Tyers

    Comparison of the Saccharomyces cerevisiae G1 cyclins: Cln3 may be an upstream activator of Cln1, Cln2 and other cyclins

    EMBO J.

    (1993)
  • F.R. Cross

    Testing a mathematical model of the yeast cell cycle

    Mol. Biol. Cell

    (2002)
  • M.E. Miller et al.

    Distinct subcellular localization patterns contribute to functional specificity of the Cln2 and Cln3 cyclins of Saccharomyces cerevisiae

    Mol. Cell Biol.

    (2000)
  • N.P. Edgington et al.

    Relationship between the function and the location of G1 cyclins in S. cerevisiae

    J. Cell Sci.

    (2001)
  • L. Dirick

    Roles and regulation of Cln–Cdc28 kinases at the start of the cell cycle of Saccharomyces cerevisiae

    EMBO J.

    (1995)
  • D. Stuart et al.

    CLN3, not positive feedback, determines the timing of CLN2 transcription in cycling cells

    Genes Dev.

    (1996)
  • K.C. Chen

    Kinetic analysis of a molecular model of the budding yeast cell cycle

    Mol. Biol. Cell

    (2000)
  • C.J. McInerny

    A novel Mcm1-dependent element in the SWI4, CLN3, CDC6, and CDC47 promoters activates M/G1-specific transcription

    Genes Dev.

    (1997)
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